Endocrine Abstracts

Waardenburg syndrome type-II is characterised by sensorineural deafness and skin/ hair hypopigmentation due to pathogenic variants in SOX10 gene. SOX10 protein is a transcription factor regulating early neural crest-cell development. Recently SOX10 pathogenic variants have been described in a small number of patients with both Waardenburg and Kallmann Syndrome (hypogonadotropic hypogonadism (HH), anosmia) indicating co-pathogenicity. An 18 year old male presented with delayed puberty. He was diagnosed with bilateral sensorineural deafness at three months and had cochlear implants. He had severe nasal polyposis, wide nasal bridge, hypo-pigmented patches of hair, learning difficulties and physical tics. His mother has mild hearing loss and maternal grandfather had heterochromia. On examination his height was 170cm (mother 167cm, father 180cm) and weight 86Kg with under-androgenised features and anosmia. Morning results demonstrated HH: testosterone 1.3 nmol/l (8.6-29), LH 3.7 IU/l (1.7-8.6), FSH 3.2 IU/l (1.5-12.4). Bone age was 14.5 years (chronological age 18.5 years). MRI was contraindicated because of cochlear implants but CT pituitary fossa was unremarkable. After counselling regarding possible behavioural change, he was started on escalating doses of testosterone treatment. On return for assessment his testosterone treatment had been stopped for 12 months (unplanned) after 12 months treatment. Morning bloods demonstrated repeatedly normal gonadal function e.g. testosterone 13.7 nmol/l, LH 9.1 IU/l, FSH 6.8 IU/l. SOX10 gene sequencing should be considered in patients with sensorineural hearing loss who develop HH. Also, detection of SOX10 mutations in new-borns with deafness and hypopigmentation should prompt hormone testing for HH during mini-puberty (first six-months). This would allow timely treatment for some, to maximise secondary characteristics and fertility potential. The natural history of patients with SOX10 pathogenic variants is not fully understood. One similar case of reversibility has been reported and suggests that re-evaluation of hypogonadism might be considered at intervals.